Impact of Vessel Suppressed-CT on Diagnostic Accuracy in Detection of Pulmonary Metastasis and Reading Time.

RATIONALE AND OBJECTIVES: To assess if vessel suppression (VS) improves nodule detection rate, interreader agreement, and reduces reading time in oncologic chest computed tomography (CT). MATERIAL AND METHODS: One-hundred consecutive oncologic patients (65 male; median age 60y) who underwent contrast-enhanced chest CT were retrospectively included. For all exams, additional VS series (ClearRead CT, Riverrain Technologies, Miamisburg) were reconstructed. Two groups of three radiologists each with matched experience were defined. Each group evaluated the SD-CT as well as VS-CT. Each reader marked the presence, size, and position of pulmonary nodules and documented reading time. In addition, for the VS-CT the presence of false positive nodules had to be stated. Cohen's Kappa (k) was used to calculate the interreader-agreement between groups. Reading time was compared using paired t test. RESULTS: Nodule detection rate was significantly higher in VS-CT compared to the SD-CT (+21%; p <0.001). Interreader-agreement was higher in the VS-CT (k = 0.431, moderate agreement) compared to SD-CT (k = 0.209, fair agreement). Almost all VS-CT series had false positive findings (97-99 out of 100). Average reading time was significantly shorter in the VS-CT compared to the SD-CT (154 ± 134vs. 194 ± 126; 21%, p<0.001). CONCLUSIONS: Vessel suppression increases nodule detection rate, improves interreader agreement, and reduces reading time in chest CT of oncologic patients. Due to false positive results a consensus reading with the SD-CT is essential.

Mitral annular calcification in the elderly - Quantitative assessment.

PURPOSE: To determine the reliability of subjective and objective quantification of mitral annular calcification (MAC) in elderly patients with severe aortic stenosis, to define quantitative sex- and age-related reference values of MAC, and to correlate quantitative MAC with mitral valve disease. METHODS: In this retrospective, IRB-approved study, we included 559 patients (268 females, median age 81 years, inter-quartile range 77-85 years) with severe aortic stenosis undergoing CT. Four independent readers performed subjective MAC categorization as follows: no, mild, moderate, and severe MAC. Two independent readers performed quantitative evaluation of MAC using the Agatston score method (AgatstonMAC). Mitral valve disease was determined by echocardiography. RESULTS: Subjective MAC categorization showed high inter-reader agreement for no (k â€‹= â€‹0.88) and severe MAC (k â€‹= â€‹0.75), whereas agreement for moderate (k â€‹= â€‹0.59) and mild (k â€‹= â€‹0.45) MAC was moderate. Intra-reader agreement for subjective MAC categorization was substantial (k â€‹= â€‹0.69 and 0.62). Inter- and intra-reader agreement for AgatstonMAC were excellent (ICC â€‹= â€‹0.998 and 0.999, respectively), with minor inconsistencies in MAC involving the left ventricular outflow tract/aortic valve. There were significantly more women than men with MAC (n â€‹= â€‹227, 85% versus n â€‹= â€‹209, 72%; p â€‹< â€‹0.001), with a significantly higher AgatstonMAC (median 597, range 81-2055 versus median 244; range 0-1565; p â€‹< â€‹0.001), particularly in patients ≥85 years of age. AgatstonMAC showed an area-under-the-curve of 0.84 to diagnose mitral stenosis, whereas there was no association of AgatstonMAC with mitral regurgitation (p â€‹> â€‹0.05). CONCLUSIONS: Our study in elderly patients with severe aortic stenosis shows that quantitative MAC scoring is more reliable than subjective MAC assessment. Women show higher AgatstonMAC scores than men, particularly in the elderly population. AgatstonMAC shows high accuracy to diagnose mitral stenosis.

Vector competence of field populations of the mosquito species Aedes japonicus japonicus and Culex pipiens from Switzerland for two West Nile virus strains.

Aedes (Hulecoeteomyia) japonicus japonicus (Diptera: Culicidae) (Theobald) is an invasive mosquito species in Central Europe, where it has colonized several areas. In this study, field-collected specimens of Ae. japonicus and Culex pipiens (Diptera: Culicidae) (Linnaeus) from Zürich (Switzerland) were orally exposed to two strains (NY99 and FIN) of the avian zoonotic pathogen West Nile virus (WNV) (family Flaviviridae, genus Flavivirus). Dissemination and transmission of the viruses after incubation for 12-15 days under a fluctuating Central European midsummer temperature regime (24 ± 7 °C) was investigated by detection of viral RNA in homogenates of pools of both head/thorax and saliva by reverse transcription real-time polymerase chain reaction (PCR). Culex pipiens was susceptible to WNV NY99 only, whereas both virus strains could be detected in Ae. japonicus, with the additional isolation of WNV NY99 in Vero cell culture from one saliva pool. Given the high abundances of Ae. japonicus in many newly colonized areas, its recently demonstrated broad host range, including mammalian and avian blood hosts, and its vector competence, this species is a potential key bridge vector of WNV in Central Europe.

Host preferences in host-seeking and blood-fed mosquitoes in Switzerland.

The avian zoonotic agent for West Nile virus (WNV) can cause neuroinvasive disease in horses and humans and is expanding its range in Europe. Analyses of the risk for transmission to these hosts in non-endemic areas are necessary. Host preferences of mosquitoes (Diptera: Culicidae), the main vectors of WNV, were determined in Switzerland using animal-baited trap (horse, chickens) experiments at a natural and a periurban site. This was undertaken on four occasions during May-September 2014. In addition, the hosts of 505 blood-fed mosquitoes collected in a zoo and in the field were determined. Mosquito data obtained in the animal bait experiments were corrected for host weight and body surface area and by Kleiber's scaling factor. Collections of 11-14 different mosquito species were achieved with these approaches. Statistically significant host preferences were identified in three species in both approaches. The other species showed opportunistic feeding behaviours to varying extents. Specifically, the invasive species Hulecoeteomyia japonica (= Aedes japonicus) was identified for the first time as feeding on avians in nature. Abundance data, spatiotemporal activity and laboratory vector competence for WNV suggested that, in addition to the main WNV vector Culex pipiens, H. japonica and Aedimorphus vexans (= Aedes vexans) are the most likely candidate bridge vectors for WNV transmission in Switzerland.

Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07).

BACKGROUND: The risk of osteoporosis and fracture influences the selection of adjuvant endocrine therapy. We analyzed bone mineral density (BMD) in Swiss patients of the Breast International Group (BIG) 1-98 trial [treatment arms: A, tamoxifen (T) for 5 years; B, letrozole (L) for 5 years; C, 2 years of T followed by 3 years of L; D, 2 years of L followed by 3 years of T]. PATIENTS AND METHODS: Dual-energy X-ray absorptiometry (DXA) results were retrospectively collected. Patients without DXA served as control group. Repeated measures models using covariance structures allowing for different times between DXA were used to estimate changes in BMD. Prospectively defined covariates were considered as fixed effects in the multivariable models. RESULTS: Two hundred and sixty-one of 546 patients had one or more DXA with 577 lumbar and 550 hip measurements. Weight, height, prior hormone replacement therapy, and hysterectomy were positively correlated with BMD; the correlation was negative for letrozole arms (B/C/D versus A), known osteoporosis, time on trial, age, chemotherapy, and smoking. Treatment did not influence the occurrence of osteoporosis (T score < -2.5 standard deviation). CONCLUSIONS: All aromatase inhibitor regimens reduced BMD. The sequential schedules were as detrimental for bone density as L monotherapy.

Combination of bevacizumab and 2-weekly pegylated liposomal doxorubicin as first-line therapy for locally recurrent or metastatic breast cancer. A multicenter, single-arm phase II trial (SAKK 24/06).

BACKGROUND: pegylated liposomal doxorubicin (PLD) and bevacizumab are active agents in the treatment of metastatic breast cancer (MBC). We carried out a multicenter, single-arm phase II trial to evaluate the toxicity and efficacy of PLD and bevacizumab as first-line treatment in MBC patients. METHODS: bevacizumab (10 mg/kg) and PLD (20 mg/m(2)) were infused on days 1 and 15 of a 4-week cycle for a maximum of six cycles. Thereafter, bevacizumab monotherapy was continued at the same dose until progression or toxicity. The primary objective was safety and tolerability, and the secondary objective was to evaluate efficacy of the combination. RESULTS: thirty-nine of 43 patients were assessable for the primary end point. Eighteen of 39 patients (46%, 95% confidence interval 30% to 63%) had a grade 3 toxicity. Sixteen (41%) had grade 3 palmar-plantar erythrodysesthesia, one had grade 3 mucositis, and one severe cardiotoxicity. Secondary end point of overall response rate among 43 assessable patients was 21%. CONCLUSIONS: in this nonrandomized single-arm trial, the combination of bimonthly PLD and bevacizumab in locally recurrent and MBC patients demonstrated higher than anticipated toxicity while exhibiting only modest activity. Based on these results, we would not consider this combination for further investigation in this setting.

[Chronic lymphocytic leukemia and loss of strength in the right arm--not a typical combination]. / Chronische lymphatische Leukämie und Kraftverlust im rechten Arm--eine nicht typische Kombination.

We report a case of metastatic renal cancer as a second malignancy in a patient with chronic lymphocytic leukemia (CLL). Six years after the primary CLL diagnosis, the clinical presentation of this patient was not typical for CLL, requiring further diagnostic steps. Due to the long-lasting course of CLL second cancers can occur in these patients. In addition some forms of tumors, such as Kaposi sarkoma, malignant melanoma, laryngeal carcinoma, lung cancer and Hodgkin Lymphoma are found more frequently in this patient population. Men with CLL have an increased risk for brain tumors, women for gastric and bladder cancers.

Capecitabine and vinorelbine as first-line treatment in elderly patients (> or =65 years) with metastatic breast cancer. A phase II trial (SAKK 25/99).

BACKGROUND: We evaluated previously established regimens of capecitabine plus vinorelbine in older patients with advanced breast cancer stratified for presence versus absence of bone metastases. PATIENTS AND METHODS: Patients > or =65 years who had received no prior chemotherapy for advanced breast cancer received up to six 21-day cycles of vinorelbine 20 mg/m(2) i.v. on days 1 + 8 with oral capecitabine on days 1-14 (1,000 vs. 1,250 mg/m(2) daily in patients with vs. without bone involvement). RESULTS: Median age was 72 years in patients with bone metastases (n = 47) and 75 years in patients without bone metastases (n = 23). Response rates were 43% (95% confidence interval, CI, 28.3-58.8) and 57% (95% CI = 34.5-76.8), respectively. Median time to progression was 4.3 (95% CI = 3.5-6.0 months) and 7.0 months (CI = 4.1-8.3), respectively. Neutropenia was the most common toxicity, with grade 3/4 occurring in 43 and 39%, respectively. Pulmonary embolism was seen in 5 and grade 3 thrombosis in 3 patients. Other toxicities were mild to moderate. CONCLUSIONS: These regimens of capecitabine and vinorelbine are active and well tolerated in patients with advanced breast cancer > or =65 years. Response rates were comparable to published results. The lower capecitabine doses appeared appropriate given the advanced age, bone involvement and prior radiotherapy.

High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer.

Studies by comparative genomic hybridization revealed that the chromosomal regions 3p25 and 8p11-p12 are recurrently amplified in bladder cancer. To investigate the prevalence of DNA copy number alterations in these chromosomal regions and study their clinical significance, we used probes for the RAF1 (3p25) and FGFR1 (8p12) genes for fluorescence in situ hybridization. A tissue microarray containing 2317 tumors was analyzed. The analysis revealed RAF1 amplification in 4.0% and FGFR1 amplification in 3.4% of interpretable tumors. In addition, deletions were found at the 3p25 locus in 2.2% and at the 8p11-12 locus in 9.9% of interpretable tumors. Both amplifications and deletions of RAF1 and FGFR1 were significantly associated with high tumor grade (P < 0.0001), advanced stage (P < 0.0001), and poor survival (P < 0.05) if tumors of all of the stages where analyzed together. RAF1 amplifications were associated with subsequent tumor progression in pT1 carcinomas (P < 0.05). The marked differences in the frequency of all of the analyzed changes between pTa grade 1/grade 2 and pT1-4 carcinomas support the concept of these tumor groups representing different tumor entities.

High-throughput tissue microarray analysis of cyclin E gene amplification and overexpression in urinary bladder cancer.

Studies by comparative genomic hybridization revealed that the 19q13 chromosomal region is frequently amplified in bladder cancer. The cyclin E gene (CCNE), coding for a regulatory subunit of cyclin-dependent kinase 2, has been mapped to 19q13. To investigate the role of cyclin E alterations in bladder cancer, a tissue microarray of 2,317 specimens from 1,842 bladder cancer patients was constructed and analyzed for CCNE amplification by fluorescence in situ hybridization and for cyclin-E protein overexpression by immunohistochemistry. Fluorescence in situ hybridization analysis showed amplification in only 30 of the 1,561 evaluable tumors (1.9%). Amplification was significantly associated with stage and grade (P: < 0.0005 each). Immunohistochemically detectable cyclin E expression was strong in 233 (12.4%), weak in 354 (18.9%), and negative in 1, 286 of the 1,873 interpretable tumors. The majority (62.1%) of CCNE-amplified tumors were strongly immunohistochemistry-positive (P: < 0.0001). The frequency of protein expression increased from stage pTa (22.2%) to pT1 (45.5%; P: < 0.0001) but then decreased for stage pT2-4 (29.4%; P: < 0.0001 for pT1 versus pT2-4). Low cyclin E expression was associated with poor overall survival in all patients (P: < 0.0001), but had no prognostic impact independent of stage. It is concluded that cyclin E overexpression is characteristic to a subset of bladder carcinomas, especially at the stage of early invasion. This analysis of the prognostic impact of CCNE gene amplification and protein expression in >1,500 arrayed bladder cancers was accomplished in a period of 2 weeks, illustrating how the tissue microarray technology remarkably facilitates the evaluation of the clinical relevance of molecular alterations in cancer.

Interactive MR-guided biopsies of the thyroid gland: validation of a new method.

The aim of this study was to demonstrate the clinical feasibility and utility of an interactive MR-guidance system to target and biopsy thyroid lesions, and to compare resolution between ultrasound and interventional MR imaging in the evaluation of thyroid lesions. Twenty thyroid lesions of 18 patients were interactively biopsied using a 0.5-T superconducting open magnet system. Stereotactic localization of the needle and imaging was accomplished using T1-weighted gradient-recalled-echo (GRE) images. Representative cytological material was retrieved in 16 of 20 lesions (benign cystic or colloid goiter: n = 14; one de Quervain's thyroiditis and one follicular neoplasia). Lesions smaller than 1.5 cm detected by ultrasound could not be visualized adequately on GRE images. Lesions smaller than 1.5 cm were successfully biopsied by ultrasound (three colloid and haemorrhagic goiters and one adenoma). Magnetic-resonance-guided interactive biopsies and positioning of non-ferromagnetic needles in the thyroid gland are technically feasible and safe. Compared with high-resolution ultrasound, lesions larger than 1.5 cm can be adequately visualized and biopsied. Magnetic-resonance-guided placement of non-ferromagnetic needles is no substitute for high-resolution ultrasound in clinical work-up of thyroid lesions.

Esthetic single-tooth replacement with implants: a team approach.

The range of indications for implant-borne prostheses in partially edentulous patients has expanded in recent years as a consequence of advances in regenerative techniques for bone and soft tissues. The esthetic demands of both patients and dentists have risen in parallel with these advances. Esthetic compromises in prostheses have become increasingly less tolerable, particularly in the anterior region of the maxilla. If the presenting situation is less than optimal, extensive preprosthetic measures may be required to prepare local tissues for acceptance of esthetically and functionally adequate prostheses. Particularly in difficult situations, collaboration by a team is recommended. The exchange of ideas and experience among specialists should begin as early as the treatment planning stage and extend over the entire course of therapy. The objective should be defined and the various steps of treatment should be coordinated with participation from all team members.

Celiac disease transmitted by allogeneic non-T cell-depleted bone marrow transplantation.

We observed the occurrence of celiac disease following allogeneic bone marrow transplantation in a patient transplanted for acute leukemia. The marrow donor was his HLA-identical sister, who had suffered from celiac disease since birth. The post-transplant period was characterized by recurrent episodes of diarrhea. Detailed workup showed atrophic intestinal mucosa on histology and anti-gliadin and anti-endomysium antibodies in the serum, features that were not present before transplantation. GVHD was absent at that time. The patient remains free of symptoms on gluten-free diet and slight immunosuppression. This case suggests transmission of celiac disease by bone marrow transplantation and supports the T cell concept in celiac disease.

Experimental cryosurgery of the liver under magnetic resonance guidance.

The feasibility and the advantages of magnetic resonance (MR)-guided interstitial cryosurgery of the liver in an 0.5 Tesla open MR system have been evaluated. Cryosurgery was performed using an Erbocryo PS system with a nonmagnetic cryoprobe of 6 mm diameter. The probe was inserted into the liver parenchyma under real-time MR control. Using continuous MR imaging two freezing cycles of 12 min each were applied. After conventional and dynamic gadolinium-enhanced MR imaging, the animals were sacrificed after 30 min, 3 hr, 24 hr, 7 days, and 21 days. Each lesion was analyzed using light microscopy. A total of seven cryolesions were made in five animals without any complications from cryosurgery. During real-time imaging, cryolesions appeared as a hemispherical growing signal loss with a mean volume of 16.4 cm3. Macroscopic volumes of the lesions showed a good correlation with dynamic enhanced MR images during follow-up, whereas real-time images usually showed an underestimation of the lesion volumes. Cryosurgery of the liver in an open-configuration MR system is a feasible and safe method. MR imaging allows the guidance and the follow-up of cryolesions of the liver with good accuracy.

[Minimally invasive surgery with MRI imaging]. / Minimal invasive Chirurgie unter MR-Bildgebung.

The main shortcoming of conventional laparoscopic procedures is the lack of a truely three-dimensional view. The development of a open-configured MR-imaging system (0.5 Tesla, General Electric, USA) with free access to the patient, allows the performance of minimal invasive procedures under MR-guidance. Advantages inherent to minimal invasive surgery can now be combined with the ideal tissue discrimination and the temperature sensitivity of MR-imaging. This new method can be used for diagnostic as well as for therapeutic interventions, especially interstitial therapy of inoperable metastases of parenchymal organs.

[Late idiopathic pneumopathy following bone marrow transplantation]. / Späte idiopathische Pneumopathie nach Knochenmarktransplantation.

4 of the 198 patients treated by bone marrow transplantation in Basel, Switzerland, with a follow-up of more than one year after therapy, developed a severe restrictive pneumopathy. In none of the 4 patients could an infectious pathogen be isolated, but all of them had signs of a chronic graft-versus-host disease. The 4 cases are described in detail.

[Flow cytometry identification of CD34-positive cells]. / Flowzytometrische Identifizierung von CD34-positiven Zellen.

In the present study three clinical applications of flow-cytometric quantification of CD34-positive cells in the field of blood and marrow transplantation are evaluated. By daily determination of CD34-positive cells in the peripheral blood after mobilization of stem cells with chemotherapy or growth-factors it is possible to set the optimal time for collection of the transplant material. Thereafter the yield of CD34-positive cells within the harvested material is determined. Finally, the efficacy of positive CD34 selection using a biotin-avidin column is evaluated. Initial experience is presented here.